Detection of recombinant Spike protein in the blood of individuals vaccinated against SARS-CoV-2: Possible molecular mechanisms

Proteomics Clin Appl. 2023 Nov;17(6):e2300048. doi: 10.1002/prca.202300048. Epub 2023 Aug 31.


Purpose: The SARS-CoV-2 pandemic prompted the development and use of next-generation vaccines. Among these, mRNA-based vaccines consist of injectable solutions of mRNA encoding for a recombinant Spike, which is distinguishable from the wild-type protein due to specific amino acid variations introduced to maintain the protein in a prefused state. This work presents a proteomic approach to reveal the presence of recombinant Spike protein in vaccinated subjects regardless of antibody titer.

Experimental design: Mass spectrometry examination of biological samples was used to detect the presence of specific fragments of recombinant Spike protein in subjects who received mRNA-based vaccines.

Results: The specific PP-Spike fragment was found in 50% of the biological samples analyzed, and its presence was independent of the SARS-CoV-2 IgG antibody titer. The minimum and maximum time at which PP-Spike was detected after vaccination was 69 and 187 days, respectively.

Conclusions and clinical relevance: The presented method allows to evaluate the half-life of the Spike protein molecule "PP" and to consider the risks or benefits in continuing to administer additional booster doses of the SARS-CoV-2 mRNA vaccine. This approach is of valuable support to complement antibody level monitoring and represents the first proteomic detection of recombinant Spike in vaccinated subjects.

Keywords: COVID-19; SARS-CoV-2; Spike protein; mass spectrometry; vaccine mRNA.

MeSH terms

  • COVID-19 Vaccines*
  • COVID-19* / prevention & control
  • Humans
  • Proteomics
  • RNA, Messenger / genetics
  • SARS-CoV-2 / genetics
  • Spike Glycoprotein, Coronavirus / genetics
  • Vaccination


  • COVID-19 Vaccines
  • spike protein, SARS-CoV-2
  • Spike Glycoprotein, Coronavirus
  • RNA, Messenger